Development and validation of novel clinical endpoints in intermediate age-related macular degeneration in MACUSTAR

Background Currently, no validated clinical endpoints for treatment studies exist for intermediate age-related macular degeneration (iAMD). Objective The European MACUSTAR study aims to develop and clinically validate adequate clinical endpoints for future treatment studies in iAMD and to identify early determinants of disease progression to late stage AMD. Material and methods The MACUSTAR study protocol was developed by an international consortium of researchers from academia, the pharmaceutical industry and medical device companies. The MACUSTAR project is funded by the Innovative Medicines Initiative 2 (IMI2) of the European Union. Results The MACUSTAR study consists of a cross-sectional and a longitudinal investigation. A total of 750 subjects with early, intermediate and late AMD as well as control subjects with no signs of AMD will be included with a follow-up period of 3 years. Overall, 20 European study centers are involved. Conclusion The MACUSTAR project will generate large high-quality datasets, which will allow clinical validation of novel endpoints for future interventional trials in iAMD. The aim is that these endpoints will be accepted as suitable for medication approval studies by the regulatory authorities and that understanding of the disease process will be improved

Effects of external nutrient sources and extreme weather events on the nutrient budget of a Southern European coastal lagoon

The seasonal and annual nitrogen (N), phosphorus (P), and carbon (C) budgets of the mesotidal Ria Formosa lagoon, southern Portugal, were estimated to reveal the main inputs and outputs, the seasonal patterns, and how they may influence the ecological functioning of the system. The effects of extreme weather events such as long-lasting strong winds causing upwelling and strong rainfall were assessed. External nutrient inputs were quantified; ocean exchange was assessed in 24-h sampling campaigns, and final calculations were made using a hydrodynamic model of the lagoon. Rain and stream inputs were the main freshwater sources to the lagoon. However, wastewater treatment plant and groundwater discharges dominated nutrient input, together accounting for 98, 96, and 88 % of total C, N, and P input, respectively. Organic matter and nutrients were continuously exported to the ocean. This pattern was reversed following extreme events, such as strong winds in early summer that caused upwelling and after a period of heavy rainfall in late autumn. A principal component analysis (PCA) revealed that ammonium and organic N and C exchange were positively associated with temperature as opposed to pH and nitrate. These variables reflected mostly the benthic lagoon metabolism, whereas particulate P exchange was correlated to Chl a, indicating that this was more related to phytoplankton dynamics. The increase of stochastic events, as expected in climate change scenarios, may have strong effects on the ecological functioning of coastal lagoons, altering the C and nutrient budgets.Portuguese Science and Technology Foundation (FCT) [POCI/MAR/58427/2004, PPCDT/MAR/58427/2004]; Portuguese Science and Technology Foundation (FCT

Science Verification for the VISIR Upgrade

The Very Large Telescope spectrometer and imager for the mid-infrared (VISIR) was upgraded in 2015 with new detectors and several new modes were added. Science Verification (SV) is carried out for new ESO instruments as well as for substantial upgrades to existing instruments. Sparse aperture masking and coronagraphy in the mid infrared have now been added to VISIR’s capabilities and during SV these new observational modes, together with the recommissioned burst mode, were used to demonstrate the observational capabilities of the instrument. The SV process for VISIR is briefly described and some results from the successful observations are presented. All SV data are publicly available

Ocean current connectivity propelling the secondary spread of a marine invasive comb jelly across western Eurasia

Aim: Invasive species are of increasing global concern. Nevertheless, the mechanisms driving furtherdistribution after the initial establishment of non-native species remain largely unresolved, especiallyin marine systems. Ocean currents can be a major driver governing range occupancy, but this hasnot been accounted for in most invasion ecology studies so far. We investigate how well initialestablishment areas are interconnected to later occupancy regions to test for the potential role ofocean currents driving secondary spread dynamics in order to infer invasion corridors and thesource–sink dynamics of a non-native holoplanktonic biological probe species on a continental scale.Location: Western Eurasia.Time period: 1980s–2016.Major taxa studied: ‘Comb jelly’ Mnemiopsis leidyi.Methods: Based on 12,400 geo-referenced occurrence data, we reconstruct the invasion historyof M. leidyi in western Eurasia. We model ocean currents and calculate their stability to match thetemporal and spatial spread dynamics with large-scale connectivity patterns via ocean currents.Additionally, genetic markers are used to test the predicted connectivity between subpopulations.Results: Ocean currents can explain secondary spread dynamics, matching observed range expansionsand the timing of first occurrence of our holoplanktonic non-native biological probe species,leading to invasion corridors in western Eurasia. In northern Europe, regional extinctions after coldwinters were followed by rapid recolonizations at a speed of up to 2,000 km per season. SourceJASPERS ET AL. | 815areas hosting year-round populations in highly interconnected regions can re-seed genotypes overlarge distances after local extinctions.Main conclusions: Although the release of ballast water from container ships may contribute tothe dispersal of non-native species, our results highlight the importance of ocean currents drivingsecondary spread dynamics. Highly interconnected areas hosting invasive species are crucial forsecondary spread dynamics on a continental scale. Invasion risk assessments should considerlarge-scale connectivity patterns and the potential source regions of non-native marine species

The Return of the Mid-infrared to the VLT: News from the VISIR Upgrade

The VLT mid-infrared imager and spectrometer VISIR returns to science operations following an extended upgrade period. Among the most important modifications are: the imaging and spectroscopic detectors have been replaced with larger AQUARIUS (1024 by 1024 pixel) detector arrays; the N-band low-resolution grating has been exchanged; and support is now provided for precipitable water vapour monitoring, in order to select the best observing conditions. The AQUARIUS detectors stem from a development for very low background applications which result in excess noise under ground-based conditions. A series of interventions was needed to find a scheme that effectively exploits these detectors for ground-based use, involving the implementation of faster chopping. VISIR has been returned to service at the VLT with enhanced capabilities

British press attitudes towards the EU's global presence:from the Russian-Georgian War to the 2009 Copenhagen Summit

This article surveys the way in which British print media have presented the European Union (EU)'s global presence in the international arena by analysing two case studies which reflect two very distinctive areas of EU foreign policy: global climate change policy and the policy towards Russia. It employs frame analysis, allowing for the identification of the way in which the discourse of the press was categorized around a series of central opinions and ideas. Frames underscore the connections made by journalists between different events, policies or phenomena and their possible interpretations. The analysis highlights that acting through the common framework of the EU rather than unilaterally was a strategy preferred by the British press. These findings are in stark contrast with the deep Euroscepticism which characterizes press attitudes towards most policy areas, and is often considered to be rooted in the British political culture, media system, public opinion or the longstanding tradition of viewing the European continent as the other

An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

BACKGROUND & AIMS: The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. METHODS & RESULTS: Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. CONCLUSION: These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases

Characterisation of Innate Fungal Recognition in the Lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung